The long term goals of this project are to determine how the genes involved in programmed cell death function in mosquitoes and to determine if this information can be used to develop new approaches in the control of mosquito populations and the spread of diseases caused by mosquito- borne microbes and viruses. Some of these diseases include malaria, dengue fever, dengue hemorrhagic fever, yellow fever and forms of viral encephalitis. To this end, mosquito genes that initiate, effect and inhibit programmed cell death will be molecularly cloned. The first step in this process will be the synthesis of cDNA libraries from RNAs of A. Aegypti metamorphic midgets. Mosquito homologues of the Drosophila activators of programmed cell death will be isolated from these libraries. To confirm that the mosquito genes are involved in programmed cell death, they will be sequenced to determine the extent of homology to the Drosophila genes. Functional tests will be performed with A. albopitus and D. melanogaster cells in culture. Once it is established that the cloned mosquito genes are involved in programmed cell death, the expression pattern of these genes during metamorphosis of the mosquito midgut will be determined. The information gained from these studies will be used to determine how best to use programmed cell death mechanisms to control mosquito populations and their ability to transmit microbes and viruses. In addition, vectors will be constructed and tested with the ultimate goal of producing transgenic mosquitoes with inducible programmed cell death genes.